Since the year 2000 alone, more than 1,000,000 vascular prosthetic devices have been implanted worldwide. From stents to artificial heart valves and ventricular assist devices, a wide range of devices are being used to treat patients often expected to live for many years after the procedures. Since biomaterials promote surface-induced thrombotic phenomena to some extent, an ever-increasing pool of patients reliant upon indefinite anticoagulant therapy has been created. This is unfortunate, as the use of drugs like heparin, warfarin and clopidogrel carries a serious risk of side effects like bleeding, bruising and serious internal hemorrhage.
Blood contacting biomaterial surfaces in particular, have been shown to adsorb a layer of proteins from blood and to attract platelets. Build-up of blood components on the surface of implanted devices may reduce their effectiveness, and in many cases will lead to serious adverse complications or operational failure. Thrombogenesis presents a major problem associated with the clinical use of all kinds of prosthetics, and the prevention of unwanted clotting without the side effects incurred through the use of blood thinning drugs would be a major advancement in the field of biomaterials.
One method for securing biomaterials against unwanted thrombosis is to modify the biomaterial surface itself. For example, anti-thrombogenic materials have been covalently bonded onto the blood-contacting biomaterial surfaces. Additionally, the biomaterial has been treated to give its surface a fixed charge which can affect the biocompatibility of the material. In other cases, the surface has been polished to an extremely high degree. Non of these techniques, however, have been completely effective in deterring platelet adhesion to the biomaterial surface.
It has been theorized that promoting adhesion of albumin to the detriment of fibrinogen at the blood-contacting surface could be effective in altering the thrombogenicity of various materials. In fact, Grunkemeier et al., Biomaterials, November, 2000 pp. 2243-2252, and Tsai et al., Journal of Biomedical Materials Research Dec. 15, 2003, pp. 1255-68, found that the amount of adsorbed fibrinogen was the chief determinant of the degree of platelet adhesion, although platelets were most attracted to a surface when a combination of proteins was residing on the surface, including Von Willebrand factor. No preadsorption of particular blood proteins has yet been shown to prevent clotting entirely. It is very difficult to prevent fibrinogen from adhering to the biomaterial surface, and only a small amount of adhered fibrinogen is necessary to start a chain reaction leading to thrombosis.
Some materials coated with anticoagulant agents such as heparin have had limited success in preventing thrombosis. However, heparin coatings will eventually dissolve over time. Drawbacks to agent-eluting surfaces have also been realized. A study by Pfisterer et al., Journal of American College of Cardiologists, Dec. 19, 2006 pp. 2592-5 regarding the Basel Stent Kosten Effektivitats Trial, Late Thrombotic Events, suggested that between 7 and 18 months after implantation, the rates of nonfatal myocardial infarction, death from cardiac causes, and angiographically documented stent thrombosis were higher with drug-eluting stents than with bare metal stents.
Overall, there have been no recognized clinical advancements that could warrant replacing traditional anticoagulation therapy. At this time, only consistent maintenance of a regimen of blood thinning agents is clinically proven to prevent the dangerous thrombotic events associated with implants.
It is a primary object of the present invention to inhibit and/or prevent thrombogenesis and blood platelet adhesion on a biomaterial surface.
It is another object of the present invention to inhibit and/or prevent blood platelet adhesion and thrombogenesis on an electrically conductive, blood-contacting surface of an implantable device.
It is a further object of the present invention to provide an anti-thrombogenic characteristic to biomaterial surfaces by providing certain blood proteins thereat.
It is a further object of the present invention to provide an anti-thrombogenic characteristic to biomaterial surfaces by providing conformationally-modified blood proteins thereat.
It is a still further object of the present invention to provide a method to pre-treat biomaterials such as pyrolytic carbon, titanium, nitinol, and stainless steel using therapeutic electrical energy so as to prevent blood platelet adhesion to the pre-treated biomaterials.